摘要
目的探讨不同剂量沙美特罗替卡松粉吸入剂(ICS/LABA)对大鼠慢性阻塞性肺疾病(COPD)气道重塑的干预作用。方法将40只Wistar大鼠随机分为对照组(A组)、模型组(B组)、低剂量ICS/LABA组(C组)、高剂量ICS/LABA组(D组)。采用烟熏加气管内注射脂多糖(LPS)法复制COPD模型,C、D组吸入中、高剂量ICS/LABA。观察肺功能和病理变化,肺泡灌洗液(BALF)中细胞计数和百分比,图像分析测量小气道平滑肌和管壁厚度,酶联免疫吸附(ELISA)法测定BALF中转化生长因子β1(TGF-β1)的表达,免疫组化法测定肺组织中基质金属蛋白酶9(MMP-9)、分泌性白细胞蛋白酶抑制剂(SLPI)的表达,实时荧光定量聚合酶链式反应(RT-PCR)检测肺组织中MMP-9mRNA的表达。结果 B组肺间质大量炎性细胞浸润,肺泡壁破坏,肺大疱形成,气管管壁和平滑肌增厚,C、D组有所减轻;B组TGF-β1、MMP-9水平与A组大鼠相比明显升高,SLPI则显著降低(P<0.05);干预后C、D组TGF-β1、MMP-9水平与B组相比明显降低,而SLPI则明显升高(P<0.05);D组TGF-β1、MMP-9阳性系数和mRNA相对含量[(82.06±4.43)(2.41±0.22)(6.156±8.86)]显著低于C组[(118.59±5.28)(3.09±0.28)(9.616±10.56)](P<0.05),而SLPI(2.95±0.28)明显高于C组(2.11±0.26)(P<0.05)。结论 ICS/LABA对COPD大鼠肺泡破坏及气道重塑有抑制作用,且高剂量优于低剂量,其机制可能与降低TGF-β1和MMP-9的表达及提高SLPI的水平有关。
Objective To evaluate the effect of different doses of salmeterol/ fluticasone（LABA/ ICS） inhalant on the air-way remodeling of chronic obstructive pulmonary disease （COPD） in rats and its possible mechanism. Methods Forty Wistarrats were divided into four groups：the control （group A）, the model （group B）, the low dose of LABA/ ICS （groups C）, and thehigh dose of LABA/ ICS （group D）. Rats were exposed to cigarette smoking daily and intratracheal instillation of lipopolysaccharide （LPS）twice daily to establish the COPD model. LABA/ ICS was inhaled to the rats of COPD models for 30 days in groups of C andD. The pathological changes in lung were observed and spirometry function was detected. The expression of TGF-茁1 in BALF wastested by ELISA. The expression of MMP-9 and SLPI in lung was determined by immunohistochemistry. The expression of MMP-9mRNA in bronchi and lung was assessed by RT-PCR. Results The inflammatory cells infiltration, alveolar wall damage, bullaeformation in lung and thickening of trachea wall and smooth muscle were found in group B, but less obvious in group C and D. Com-pared to group A, group B had higher expression of MMP-9 and TGF-β1 level,but lower SLPI （P〈0. 05）. After intervention withICS/ LABA,both MMP-9 mRNA expression and TGF-β1 level were dramatically decreased,but SLPI was increased in group C and Dcompared with group B（P〈0. 05 ）. The TGF-β1 , MMP-9 and its mRNA in group D[（82.06±4. 43）, （2. 41±0. 22）, （6. 156±8.86）]were lower than group C[（118. 59±5. 28）, （3. 09±0. 28）, （9. 616±10.56）], the SLPI（2. 95±0. 28） was much higherthan group C（2.11±0.26）. Conclusion ICS/ LABA inhibits the airway wall remodeling of the COPD rats in a dose-dependentmanner, which may be associated with upregulation of TGF-β1 and MMP-9 expression and elevation of SLPI.
出处
《医药导报》
CAS
北大核心
2014年第3期318-322,共5页
Herald of Medicine
